The mechanism of the hypoglycemic action of gliclazide was evaluated in 17 diet-treated non-insulin-dependent diabetes mellitus (NIDDM) patients. In study A, five patients received a 240-minute glucose infusion along with [3-3H]glucose infusion. In study B, seven patients received a 240-minute isoglycemic insulin clamp along with [3-3H]glucose infusion. And in study C, five patients received a somatostatin infusion with basal replacing doses of insulin and glucagon. The three studies (A, B, and C) were repeated twice. Gliclazide (240 mg orally) was administered on one occasion, and placebo was given on the second occasion. Basal hepatic glucose production (HGP) and utilization and plasma glucose, insulin, C-peptide, glucagon, and free fatty acid (FFA) concentrations were similar before administration of gliclazide and placebo. In study A, plasma glucose, its incremental area, and HGP were reduced by gliclazide administration (all P < .05), but glucose utilization was not significantly affected. The increase in plasma insulin and C-peptide concentrations was similar with gliclazide and placebo, although the plasma insulin to glucose ratio was increased with gliclazide. HGP decremental area was correlated with the reduction in plasma glucose incremental area (r = -.63, P < .05). In study B, gliclazide administration produced a larger suppression of HGP, but the overall rate of glucose utilization was not different in the two studies. In study C, plasma glucose concentration and HGP progressively decreased in both studies, without a difference between gliclazide and placebo. These results suggest that under conditions of hyperglycemia and hyperinsulinemia gliclazide elicits a larger suppression of HGP
Gliclazide potentiates suppression of hepatic glucose production in non-insulin-dependent diabetic patients
DEL PRATO, STEFANO
1996-01-01
Abstract
The mechanism of the hypoglycemic action of gliclazide was evaluated in 17 diet-treated non-insulin-dependent diabetes mellitus (NIDDM) patients. In study A, five patients received a 240-minute glucose infusion along with [3-3H]glucose infusion. In study B, seven patients received a 240-minute isoglycemic insulin clamp along with [3-3H]glucose infusion. And in study C, five patients received a somatostatin infusion with basal replacing doses of insulin and glucagon. The three studies (A, B, and C) were repeated twice. Gliclazide (240 mg orally) was administered on one occasion, and placebo was given on the second occasion. Basal hepatic glucose production (HGP) and utilization and plasma glucose, insulin, C-peptide, glucagon, and free fatty acid (FFA) concentrations were similar before administration of gliclazide and placebo. In study A, plasma glucose, its incremental area, and HGP were reduced by gliclazide administration (all P < .05), but glucose utilization was not significantly affected. The increase in plasma insulin and C-peptide concentrations was similar with gliclazide and placebo, although the plasma insulin to glucose ratio was increased with gliclazide. HGP decremental area was correlated with the reduction in plasma glucose incremental area (r = -.63, P < .05). In study B, gliclazide administration produced a larger suppression of HGP, but the overall rate of glucose utilization was not different in the two studies. In study C, plasma glucose concentration and HGP progressively decreased in both studies, without a difference between gliclazide and placebo. These results suggest that under conditions of hyperglycemia and hyperinsulinemia gliclazide elicits a larger suppression of HGPI documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
